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THE 



ORIGIN AND PROPAGATION OF 
DISEASE. 



AN ANNIVERSARY DISCOURSE, DELIVERED BEFORE 

THE NEW YORK ACADEMY OF MEDICINE, 

NOVEMBER 20, 1873. 



gjg 



JOHN C. DALTON, M. D., 

PROFESSOR OF PHYSIOLOGY IN THE COLLEGE OF PHYSICIANS AND SURGEONS, NEW YORK. 



[PUBLISHED BY ORDER OP THE ACADEMY.] 



NEW YOEK: 

D. APPLETON ANT) COMPANY, 

549 & 551 BROADWAY. 

1874. 



\ 



^ 







OFFICERS AND TIME OF SERVICE 

President. 

AUSTIN FLINT, Senior, M. D., 1873-'75. 

Vice-Presidents. 
WILLIAM C. ROBERTS, M. D., 1873-'74. 
SAMUEL S. PURPLE, M.D., 1872-'75. 
SAMUEL T. HUBBARD, M.D., 1873-'76. 

Recording Secretary. 
WILLIAM T. WHITE, M. D., 1871-'74. 

Assistant Recording Secretary. 
WILLIAM H. B. POST, M. D., 187l-'74. 

Corresponding Secretary. 
JOHN G. ADAMS, M. D., 187l-'74. 

Treasurer. 
JAMES O. POND, M. D., 187l-'74. 

Librarian. 
JOHN H. HINTON, M. D. 

Trustees. 
JAMES L. BANKS, M. D., 1869-'74. 
JAMES ANDERSON, M.D., 1870-'75. 
ALFRED UNDERHILL, 1871-'76. 
ISAAC E. TAYLOR, M. D., 1872-'77. 
EDMUND R. PEASLEE, M. D., 187 3-' 7 8. 

Publication Committee. 
EDMUND R. PEASLEE, M. D. 
SAMUEL S. PURPLE, M. D. 
WILLIAM T. WHITE, M.D. 



ANNIVERSARY DISCOURSE. 



Mr. President and Fellows of the Kew York Academy 
of Medicine: 

The anniversary meeting of the Academy of Medicine 
may be regarded as a sort of annual conference, in which one 
of its members is deputed to offer to the Academy a short 
address upon some topic of general professional interest, and 
more or less appropriate to the time. Perhaps we can hardly 
employ the occasion to-night in a more suitable way than by 
endeavoring to see what, on the whole, is the direction in 
which medical thought is now most active ; to cast the pro- 
fessional horoscope, so to speak, for the present, and to antici- 
pate, as nearly as may be, what we are to expect from it in 
the immediate future. 

Not that we should be willing to claim the gift of prophecy, 
or to place too much confidence in delusive flights of the ima- 
gination. Medicine is essentially a skeptical science, and very 
properly regards with disapproval any thing which claims her 
attention without offering, at the same time, unmistakable 
guarantees of respectability. But there may be a kind of an- 
ticipation which is really a scientific one. "Within the past 
two or three years we have seen our own Meteorological Bureau 
triumph over what was proverbially the most difficult of all 
popular puzzles, aud foretell the weather of each day with a 
certainty which has excited our surprise and admiration. With 



6 

telegraph-lines from all over the continent converging to the 
central office at Washington, the chief of the Bureau can trace, 
from hour to hour, the progress of a meteorological change, 
moving, with uniform or accelerated speed, from St. Paul to 
Milwaukee, from Milwaukee to Detroit, from Detroit to Buf- 
falo ; and he knows that within a given period it will reach 
New York, with almost as much certainty as though he stood 
on the top of a watch-tower and saw it coming. Within such' 
limits as these it may perhaps be allowable sometimes to in- 
dulge in surmises, even in the strictest and most exacting of 
the natural sciences. 

Is there any thing in the aspect and condition of any part 
of medicine to-day that looks like a change in the scientific 
barometer ? Can we see such a tendency in the medical mind, 
at present, as would suggest what may fairly be called a new 
movement — in which successive ideas and discoveries are not 
only accumulating as heretofore, but in which they also seem 
to be taking, or about to take, a new interpretation ; so as to 
give expression, in definite terms, to a doctrine which has here- 
tofore had only a vague and uncertain existence ? 

If there be any one direction in which progress is now so 
marked as to constitute a dominant feature of the present state 
of medicine, and to embrace a practically new medical idea, 
I should say it was that of the origin and propagation of 
disease by independent organic germs. Perhaps it would be 
wrong to say that this doctrine is even yet distinctly formu- 
lated. It is certainly far from being definitely established as 
a general truth. Some very wild and reckless statements have 
been made in regard to it, by observers possessed of more zeal 
than knowledge ; and some elaborate but baseless theories re- 
lating to the specific development and transformation of organic 
germs have been tried at the bar of scientific investigation, and, 
being convicted of incompetency, have suffered, accordingly, 
the just penalty of extermination. Perhaps the doctrine itself 
will also be finally abandoned. It may be that the evidence 
in its favor, which is yet only partial, will hereafter lose its 
special significance ; and the appearances which now seem to 



sustain it may come to be naturally explained in some other 
way. Still, there can be no doubt that the idea is at present 
entertained, and that it is by no means confined to the minds 
of careless or irresponsible theorizers. So far, it exists in the 
form rather of a scientific instinct than of a positive belief; 
and its gray light hangs about the edge of the medical horizon 
like the coming dawn of a new period. 

Isow, can this instinct of the medical mind be justified in 
any way ? Are there any facts and discoveries, already estab- 
lished beyond the possibility of doubt, which have naturally 
led it in this direction, and which point, like the telegraphic 
reports of successive meteorological stations, to a continuous 
and definite movement of scientific pathology ? 

I think it really began many years ago, in the early inves- 
tigation of parasitic diseases. Perhaps we can hardly include 
under this designation the effects produced by ordinary intes- 
tinal worms, like taenia or ascaris, because the animal and para- 
sitic nature of these worms was perfectly palpable, and could 
not be mistaken by any one. l&ut^scdbies was on a different 
footing. It was a contagious, eruptive affection, capable of 
spreading over a large portion of the body, and of giving the 
patient great discomfort ; and, when it was found to be due 
simply to the presence and propagation of a parasitic insect, 
the discovery was a great achievement, and for the first time 
made it possible to have a distinct and rational comprehension 
of the origin of the disease, as well as of its propagation and 
means of cure. A remarkable circumstance in the history of 
our knowledge in regard to Sarcoptes scabiei is, that its dis- 
covery in the present century was in fact a rediscovery of 
something which had been known centuries before and long 
forgotten ; or, at least, the method of finding the insect having 
been lost, the most eminent dermatologists of forty years ago 
had never seen it, and were really in doubt as to its existence. 
However, this uncertainty was terminated in 1834, by the 
Corsican student Eenucci, and the study of its structure and 
development was afterward accomplished by Raspail and 
Bourguignon ; so that our knowledge, both of the disease and 
its parasite, was then placed upon a permanent footing. 



Perhaps the most suggestive part of this discovery related 
to the reproduction of the parasite, the manner in which the 
female lays her eggs in galleries excavated in the skin, and 
the time required for the hatching and dispersion of the young, 
because this showed a direct connection between the local 
spread of the disease and the increase, by ordinary sexual gen- 
eration, of the young brood of the parasite. However, there 
was nothing very remarkable in the mode of this generation. 
The eggs of the female were deposited and hatched in the 
usual way, and the young sarcoptes came to resemble their 
parents after a very short and regular period of development. 

But ten or fifteen years later a discovery was made with 
regard to some of the internal parasites which had a charac- 
ter of unexpected peculiarity : that was, the specific identity of 
two parasites formerly supposed to be distinct, namely, cysti- 
cercus and trenia. These two worms — so unlike in their size, 
their general configuration, and even in the species of animal 
which they inhabit — were shown \>y the researches of Siebold 
and Kuchenmeister to be only different stages of growth of 
the same creature — one the encysted and quiescent, the other 
the intestinal and reproductive form. The well-known experi. 
ments carried on in this investigation showed furthermore the 
regular and natural conversion of these two forms into each 
other ; and thus we came fully to understand that the exist- 
ence of tape-worm in man was owing to his having eaten 
measly pork containing cysticercus, and that the pig became 
contaminated with cysticercus by devouring the eggs or the 
egg-bearing articulations of tasnia solium. The knowledge of 
the alternation of generations and of the migration of para- 
sites from one habitat to another at different periods of their 
development became in this way connected with the pathology 
and mode of propagation of certain well-known and perfectly 
distinct morbid affections. 

But so far, perhaps, these morbid affections hardly deserved 
the name of diseases. They were simply local disorders, due 
to the presence of a parasitic intruder in the substance of the 
skin or in the cavity of the intestinal canal. It was another 



9 

thing, to learn, some years later, that a microscopic parasite 
might diffuse itself generally throughout the system, and thus 
give rise to a rapid and fatal train of symptoms hardly dis- 
tinguishable from those of any febrile constitutional disease. 
No doubt cases of infection by Trichina spiralis have always 
occurred, as frequently as they do now. But previous to the 
year 1850 the milder ones in all probability were supposed to 
be rheumatic in their origin, while the fatal cases passed for 
fevers of a typhoid character. There were even epidemics of 
the trichinous affection, as there are of typhoid fever and in- 
fluenza ; and, when the true character of the disease became 
known, it was perfectly evident how these epidemics origi- 
nated and exactly how far they might extend. Each one was 
commenced by the slaughter and preparation for food of a 
trichinous pig ; and the patients affected were precisely those 
who had introduced into their systems ever so small a portion 
of the infectious food. 

In this instance, also, there was found to be an unexpected 
relation between two different forms of the same parasite. 
Trichina spiralis had been known since 1830 : but it had yet 
been seen only in its quiescent, encysted form, embedded in 
the muscular tissue, without movement or reproduction. Con- 
sequently, though we were familiar with the worm itself, we 
knew nothing of the disease produced by it. Its new growth 
and active reproduction in the intestinal canal, the swarming 
emigration of its innumerable progeny, and the constitutional 
symptoms which followed, were a new revelation, and showed 
that the whole system, as well as a particular organ or tissue, 
might suffer from the effects of parasitic contamination. 

In all the affections which have now been enumerated, the 
parasite is one of an animal nature, with regular generative 
apparatus and active sexual reproduction. But the last thirty 
years have seen a very remarkable advance also in our knowl- 
edge of the vegetable parasites. This has naturally coincided 
with a similar activity among scientific botanists in the study 
of the simpler forms of vegetation, the cryptogam ic plants in 
general, and particularly of the microscopic fungi and algas. 



10 

A. little over half a century ago the species of flowering plants 
described by botanists were much more numerous than the 
cryptogams ; but now the proportions of the two classes are 
reversed. In 1818, according to Mr. Cooke, 1 an eminent Brit- 
ish botanist, " less than eighty of the more minute species of 
fungi, but few of which deserved the name of microscopic, 
were supposed to contain all then known of these wonderful 
organisms. Since that period microscopes have become very 
different instruments ; and one result has been the increase of 
the 564 species of British fungi to 2,479. By far the greater 
number of the species thus added depend for their specific 
characters upon microscopical examination. At the present 
time the number of British species of flowering plants scarcely 
exceeds three-fourths of the number of fungi alone, not to 
mention ferns, mosses, alga?, and lichens." 

A large proportion of these microscopic plants are para- 
sitic upon other organisms ; and for the earliest study of them, 
as connected with disease in the human subject, we are indebted 
to the dermatologists. 

The first discovery of parasitic vegetation in cutaneous 
affections was by Schonlein, in 1839, 2 who found in the crust 
of favus cryptogamic vegetable filaments ramifying in the 
diseased growth. In 1841 Gruby made a similar observa- 
tion, 3 and described accurately both the mycelium filaments 
and the spores. He asserted them to be always present 
in cases of favus, and declared that the malady itself was 
essentially " nothing but a vegetation." The parasite thus 
described proved to be the same with that previously seen by 
Schonlein, and it was at last definitely known by the name of 
Achorion Schonleinii. 

Gruby continued his examinations, and in 1844 discovered 
a microscopic vegetation growing upon the skin, in a case of 

1 "Introduction to the Study of Microscopic Fungi," London, 1870, 
p. 45. 

2 Miiller's Arcliiv for 1839 ; cited in Robin," Vggetaux Parasites," Paris, 
1853, p. 477. 

3 " Coraptes Rendus de rAcad&nie des Sciences," 1841, tome xiii., pp. 
72, 309. 



11 

porrigo decalvans ; * and the same parasite, the Trichophyton 
tonsurans, has since been recognized as a constant accompani- 
ment of tinea sycosis and tinea circinnata. 

Finally, Microsporon furftir was discovered by Eichstedt, 
in 1846, 2 as a parasitic vegetation in tinea versicolor; so that 
within ssven or eight years three distinct microscopic fungi 
were discovered and recognized as occurring in diseased con- 
ditions of the human skin. 

ISTow, the first question which naturally came up in rela- 
tion to the discovery was this : Is the microscopic fungus the 
cause of the disease, or is the disease the cause of the fungus ? 
Either of these two suppositions might be the true one. In 
the first place, the fungus, by its accidental presence and 
growth in the skin, might excite all the irritation and morbid 
discharges characteristic of the malady. On the other hand, 
its presence might be altogether secondary, and a result of the 
morbid action instead of its cause. Every vegetable requires 
a soil suited to its growth. The fungus-germs might be in- 
capable of fastening themselves upon the healthy skin, but 
might readily flourish in the decomposing mixture of inflam- 
matory exudations. This question, in the earlier stages of the 
investigation, presented a real difficulty. Henle, in 1840, 
believed that Achorion Schonleinii was merely an incidental 
formation in the crust of favus, while Remak and others re- 
garded it as the cause and essential element of the disease. 

Now, how was this difficulty to be settled ? If tinea ton- 
surans is always accompanied by trichophyton, and if tricho- 
phyton is never found upon the skin, except in some form of 
tinea, how can we tell which of these two is the cause and 
which the consequence of the other? 

The test of this is twofold : 1. Inoculation of the parasite 
and reproduction of the disease ; 2. Destruction of the parasite 
and cure of the disease, 

Both of these tests have been successfully carried out. 
The inoculation of Achorion Schonleinii was accomplished by 

1 " Oomptes Eendus de l'Acad<knio des Sciences," tome xviii., p. 583. 
a Cited in Robin's " Vegetaux Parasites," Paris, 1853, p. 438. 



12 

Kemak, 1 in 1340, and subsequently by Bennett, 8 Hebra, 
Vogel, Bazin, 3 Kobner and Deffis ; that of Trichophyton by 
Denis 4 and Kobner ; 5 and, finally, that of Microsporon, by 
Kobner, 6 in 1864. The fungus-spores, transplanted upon the 
skin of other individuals, or upon other parts of the skin of the 
patient, after a certain interval germinate and multiply, and 
so create a secondary focus of the disease. The contagious 
character of the malady is thus seen to depend, not upon a 
virus, in the old sense of the word, but upon the actual com- 
munication of reproductive germs, which give origin in their 
new location to a vegetative growth similar to the old. The 
vegetable growth, therefore, precedes the disease, and must 
be regarded as its cause rather than its consequence. 

The actual transportation of these germs through the air 
is also a matter of demonstration. Lemaire 7 placed glass jars 
filled with ice in a shallow basin, so that the condensed moist- 
ure of the atmosphere, deposited upon the cold sides of the 
glass, might trickle down and collect in the basin below. He 
then applied friction to the head of a boy with favus, near by, 
and found that the spores of achorion were floated by the 
air-currents for a distance of twenty inches into contact 
with the jars ; and then, being entangled by the condensed 
moisture, were carried down into the basin. He sometimes 
found as many as thirty spores in a single drop of condensed 
moisture. 

The second part of the test is equally well established. 
I presume that dermatologists are now fully agreed that, for 
all cutaneous affections known to be characterized by the 
presence of a microscopic fungus, the one essential element of 

1 Cited in Robin; "Veg6taux Parasites," Paris, 1853, p. 477. 

2 "Principles and Practice of Medicine," New York, 1867, p. 850. 

3 "Affections cutanees parasites," Paris, 1858, p. 56. 

4 Bazin, "Affections cutanees parasites," p. 147. 
6 Schmidt's " Jaljrbiicher," cxxvi., p. 260. 

6 Cited in Neumann's "Handbook of Skin Diseases," translated by 
Dr. L. D. Bulkley, New York, 1872, p. 434. 

7 "Comptes Eendus de l'Academie des Sciences," 1864, tome lix., 
p. 127. 



13 

cure is the application of some parasiticide which shall destroy 
the vitality of the fungus. Iodine, sulphurous acid, or mer- 
curial bichloride, by killing the vegetable, as sulphur-ointment 
kills the animal parasite of scabies, in simpler cases absolutely 
puts an eud to the disorder, and in the more complicated ones 
leaves behind only secondary symptoms, which have no longer 
any specific or contagious character. Of course there are 
various points relating to these affections which are still more 
or less in doubt. Some microscopic cutaneous fungi have 
been described as distinct species, which have not received 
general recognition, and some observers are disposed to ques- 
tion whether the three principal ones may not all be simple 
varieties or forms of development of the same plant. 

But there are similar points of difference still existing 
among scientific botanists with regard to microscopic fungi 
in general ; and I believe that the three principal facts of (1) 
specific parasitic vegetation as a cause of cutaneous disease ; 
(2) its propagation by the transport and germination of spores ; 
and (3) its treatment and cure by parasiticide applications, 
may now be regarded as wholly beyond a reasonable doubt. 

I have already alluded to the remarkable activity of bo- 
tanical research of late years in the department of cryptogamic 
vegetation. The most striking results have been attained by 
these investigations, in increased knowledge of the modes of 
development and reproduction of these organisms. The phe- 
nomena of the so-called alternation of generations and of 
migration from one habitat or locality to another, are by no 
means confined to animal parasites. On the contrary, the 
most remarkable instances of both are to be found in cryp- 
togamic vegetables. Fungi formerly regarded as distinct 
species, and even as belonging to different genera, are seen 
to be successive forms of the same plant, following each other 
in definite order through the regular cycle of their annual 
reproduction. 

The three fungi, known as Trichdbasis, Puccinia, and 
jEcidium, appear in succession, as different members of the 
same specific generation, upon the cereal grains in summer 



14 

and in autumn, and upon the barberry in the spring; while 
corresponding differences are to be seen in their spores and 
mode of germination at these different epochs. 

It would perhaps be difficult to imagine a scientific pur- 
suit less likely to produce any thing of value for practical med- 
icine than the study of microscopic fungi growing as parasites 
upon other vegetables. And yet, if it should finally turn out 
that these minute researches are preliminary to the discovery 
of a means for preventing or controlling an epidemic of scar- 
latina, we can say with truth that such a result would not be 
more remarkable than many which have actually followed from 
purely scientific investigations in chemistry and physics. 

At all events, it is certain that these botanical discoveries 
have had an important influence in directing medical research 
in the path which it is now following. It could hardly be 
otherwise, from the moment they were found to have a direct 
connection with certain epidemic diseases in the vegetable 
world, some of which are of great practical consequence to 
us, as affecting the annual supply of food. 

Let me remind you of the history of our knowledge in re- 
gard to the disease known as potato-rot. 

This disease first made its appearance, so far as we know? 
about thirty years ago. The most destructive season of that 
epidemic in this country was in 1844. 1 Previously to that 
time, the annual crop of potatoes in the United States 
amounted to over one hundred million bushels ; but, in conse- 
quence of the blight, it was reduced in some parts of the coun- 
try to one-half or even to one-quarter of the ordinary yield. 2 

In 1845, it showed itself in England, Scotland, and Ireland, 
and spread with great rapidity. This is the account of it 
given by Mr. Cooke, 3 one of the highest authorities on that 
subject : 

1 American Quarterly Journal of Agriculture and Science, January, 
1845. 
^- " Patent-Office Reports, Department of Agriculture," 1856. 

3 " Introduction to the Study of Microscopic Fungi," London, 1870, pp. 
144, 146. 



15 

" It first appeared in the Isle of Wight, in the middle of 
August; a week afterward, it had become general in the 
south of England, and at the end of a fortnight there were but 
few sound samples of potatoes in the London market. The 
course of the disease was this: In the month of July or 
August the leaves of the vines would be suddenly seen to be 
marked with black spots. They then began to wither, and 
give off an offensive odor, and the disease spread so rapidly 
that the whole vine would be blighted in a few days, and a 
field, which had before been covered with a luxuriant growth, 
at the end of a fortnight was merely a scene of desolation, and 
looked as if it had been struck by a severe frost. If the pota- 
toes were immediately dug out of the. ground, many of them 
were found already partially decayed, or touched with brown- 
ish and softened spots." 

The disease broke out again in 1854 and 1855, and was 
destructive in the State of New York, in Rhode Island, Massa- 
chusetts, Ohio, Illinois, and at various other points ; 1 and about 
1865, or ten years later, it made its appearance for a third 
time. I am told by an old and experienced farmer of Wash- 
ington County, New York, that in 1861 and 1865 the potato 
crop in that region was practically destroyed ; so that often in 
a twenty-acre field there would not be a single good potato. 
Potatoes were usually to be had at that place for seventy-five 
cents per bushel, but in those years they were in some cases 
sold at eight dollars per bushel, for farmers' consumption. 

This destructive malady was at last found to be due to the 
ravages of a microscopic fungus, called, from its mode of fruc- 
tification and its injurious effects, the Peronospora infestans. 

The fungus has a mycelium of fine, cylindrical, ramifying 
tubes. Its fructifying part consists of filaments which stand 
up vertically from the mycelium, dividing at the end into four 
or five branches, and each branch bears upon it several succes- 
sive swellings, making a kind of sausage-like chain, whence its 
name of " Peronospora." At the end of each chain there is a 

1 " Patent-Office Reports, Department of Agriculture," 185G ; " Massa- 
chusetts State Board of Agriculture," 1856. 



16 

complete oval spore, and the spore, when ripe, detaches itself 
and germinates, to produce again a new mycelium. 

When the peronospora is placed in contact with the leaves 
of a potato-vine, its filaments penetrate into and through the 
epidermic cells, and so reach the intercellular tissue of the leaf 
and stem ; and there they continue to grow, producing a rapid 
withering and blight. When the parasite has attained a cer- 
tain growth, it begins to fructify. Its upright filaments burst 
through the pores of the leaves, and are crowned with the 
characteristic chain of spores. Each spore, when ripe, if sup- 
plied with moisture, produces six or seven secondary zoo- 
spores, armed with long vibrating cilia, and capable of a rapid 
spontaneous motion. After moving about for a short time, 
the zoospore becomes quiescent, throws out an elongated fila- 
ment, and germinates afresh. 

It is no doubt in this way that the germ of the parasite 
reaches the tuber of the potato at the root of the vine. For, if 
sound potatoes be placed in the ground, and the surface of the 
soil be sprinkled with the spores of peronospora, and then 
watered from time to time, the potatoes are found to be in- 
fested with the disease in about ten days. 1 

So the fructification of the fungus naturally takes place 
upon the surface of the leaves of the potato-vine. The spores 
fall off, are carried by the rain into and through the soil, and 
so reach the potatoes beneath. Next year, when the infected 
potato-eyes are planted, germination begins again, the 
mycelium filaments grow upward through the stem and 
leaves, and in July or August fructification appears on the 
exterior as before. 

This species affords a good example of the extreme fecun- 
dity of the parasitic fungi. It has been estimated that, on the 
under surface of a potato-leaf, one square line is capable of 
producing over three thousand spores. Each spore supplies 
at least six zoospores ; so that from one square line we may 
have nearly twenty thousand reproductive bodies, each capa- 

1 Eobin, " Traitd du Microscope," Paris, 1871, p. 967. 



17 

ble of originating a new mycelium ; and a square inch of sur- 
face may yield nearly three million such bodies. 

The mycelium filaments can penetrate the cellular tissue of 
a leaf in twelve hours, and, when established there, may grow 
and bear fruit in eighteen hours longer, while the spores are 
perfected and ready to germinate in twenty-four hours after 
they have been detached and placed in water. This fully ex- 
plains the rapidity with which the disease is known to spread. 

The subject of internal vegetable parasites is of the greater 
importance, because we now know that they may attack ani- 
mals as well as plants. The best illustration of these affections 
is perhaps the disease which, under the name of pebrine, has 
been so destructive to the silk-worm in France. Eight or ten 
years ago its effects were so serious that, in 1865, the annual 
production of silk in that country was reduced to less than 
one-sixth of its former average, and the loss in money value 
for that year alone amounted to twenty million dollars. 1 It 
was due entirely to the influence of a microscopic vegetation, 
which destroyed the silk-worm, and was readily communicated 
to the neighboring broods. 

It is plain, therefore, that the study of parasitic diseases, 
for many years, has been increasing in development and be- 
coming of greater importance in general pathology. From 
being confined, as at first, to a few cases of local disorder, it 
has now come to embrace a great variety of morbid affections. 
It has demonstrated the close connection existing between ani- 
mal and vegetable pathology, and it has shown that severe 
and even fatal constitutional disorders of the animal frame 
may result from the internal growth of microscopic parasites 
of a vegetable nature. And these facts have been ascertained 
by patient microscopic investigation, and laborious experiment 
on the development of eggs and spores, and the phenomena 
of infection and contagion. It cannot be denied that the re- 
sults, so far, are genuine. 

"We now come to a part of the subject which may seem to 
be less directly connected with medical doctrines ; and yet it 

1 Tyndall, " Fragments of Science,' 1 New York, 1872, pp. 288. 

2 



18 

is one which, if it really have a bearing on pathology, gives to 
the whole question a character of still greater importance. 
That is, the true nature of the process of fermentation. 

The more essential phenomena of fermentation have been 
known from time immemorial. If we add to a solution of 
sugar, or to any clear vegetable juice containing sugar, a small 
portion of yeast, and keep the mixture in a moderately warm 
place, after a few hours of apparent inactivity, certain remark- 
able changes take place it : 1. The liquid becomes uniformly 
turbid. 2. It is more or less agitated by minute bubbles of 
ga», which are generated in its interior, rise to the surface, 
and escape there. 3. The sugar gradually disappears from 
the solution, and alcohol takes its place. 4. When all the 
sugar has been thus consumed, the gas-bubbles cease to rise, 
the liquid again becomes clear and quiescent, its turbid con- 
tents being slowly deposited in a whitish layer at the bottom ; 
and, 5. This deposit is found to be itself a layer of yeast, often 
much greater in quantity than that originally added, and ca- 
pable of exciting the same kind of fermentation in another 
saccharine liquid. 

Beside this, chemical investigation has shown that the gas 
evolved is- carbonic acid, and that the weight of the sugar 
which disappears is accounted for, within reasonable limits of 
accuracy, by that of the carbonic acid and alcohol produced, 
with a little glycerine and succinic acid formed at the same 
time. It is therefore a chemical transformation, in which the 
elements of the sugar are separated from their combination, 
and rearranged to form other non-nitrogenous compounds. 

But it is a chemical change which will not take place spon- 
taneously. It requires the presence of yeast artificially added, 
or of a natural ferment, present in the vegetable juice. The 
theory of fermentation formerly in vogue was, that the nitro- 
genous matter in solution in the yeast excited, by its own 
molecular changes, the decomposition of the sugar ; taking by 
itself no direct part in the chemical phenomena, and neither 
absorbing nor discharging any of the materials of the solution. 

In enumerating these facts I do not always follow the ex- 



19 

act chronological order in which they were discovered, nor do 
I wish to take up. your time in alluding to all the details and 
varieties of fermentation. It will be sufficient for our present 
purpose to bear in mind simply the main features of the pro- 
cess, namely, the addition of ferment to a saccharine liquid, 
turbidity of the solution, decomposition of the sugar, appear- 
ance of alcohol and carbonic acid, and, finally, reproduction 
of the ferment. 

Two hundred years ago Mr. Anthony Leeuwenhoeek was 
investigating all sorts of natural objects with his newly-con- 
structed microscopes, consisting each " of a very small double 
convex glass, let into a socket between two silver plates." He 
examined the blood-globules, the capillary vessels, the sper- 
matic corpuscles, the structure of wood, of hair, of teeth; and 
with the same instruments he saw in yeast little globules col- 
lected into groups of three or four together. 1 But he had too 
many other novelties, all attracting his attention together, to 
spend much time on any one of them, and he did not learn the 
nature or specific characters of the globules of yeast ; he only 
determined the bare fact of their existence. 

But in 1837 the French chemist Cagniard-Latour a examined 
the yeast-globules with more care. He measured their size, 
and found them to be at most ^Vb" °f an i° cn * n diameter. 
He declared that they were of a vegetable nature, and that 
they multiplied by the process of budding. He called atten- 
tion to the fact that during the fermentation of beer the fer- 
ment increases in quantity, producing at the end of the pro- 
cess six or seven times as much yeast as was introduced at the 
beginning ; and he first broached the idea that " it is probably 
by some effect of their vegetation that the yeast-globules de- 
stroy the equilibrium of the elements of the sugar." 

The theory, however, was at that time premature, and it 
did not meet with general acceptance. The existence of the 
yeast-plant, so far as then known, was an isolated fact, confined 
to the single case of fermenting beer. The opposite theory, of 

1 "Philosophical Transactions," 1081, p. 507. 

3 li AnnalesdeChitnie et de Physique," 1838, tome lxviii., p. 216. 



20 

the catalytic action of an albuminous liquid, was maintained 
by Liebig with all the force of his remarkable genius, and 
was consequently almost universally adopted. The yeast-plant 
was thought to be an incidental growth in the fermenting fluid, 
and not to have auy direct or important connection with the 
process itself. 

About fifteen years ago a new epoch was inaugurated in 
the history of fermentation by the brilliant researches of Pas- 
teur. The existence and growth of a fungoid vegetation were 
now found not to be confined to the single case of beer-yeast, 
but to be a general fact common to the alcoholic fermentation 
of beer, wine, and bread, and also to a variety of other kinds, 
such as the viscous, butyric, and acetic fermentations. The 
fungus itself was industriously studied in its different genera 
and species, with their specific modes of growth and reproduc- 
tion, like those of any other natural family of plants ; so that 
the Saccharomyces cerevisice, or the yeast-fungus of beer, can 
now be distinguished from the other species of alcoholic fer- 
ments, as well as from the fungi of other kinds of fermenta- 
tion. 

The different view thus introduced is most distinctly ex- 
pressed by Pasteur himself. " According to the old theory," 
he says, " fermentation is a process correlative with death, and 
depends on the decay of albuminous matter ; according to the 
new one, it is correlative with life, that is, the active growth 
and development of the fungous vegetation. . . . The yeast- 
globules are actual living vegetable cells, capable of producing 
the transformation of sugar, just as the cells of the mammary 
gland in a living animal transform the ingredients of the blood 
into the ingredients of the milk." 

The discussions on this subject, which lasted for ten years, 
took a very wide range, and especially became connected with 
the kindred topic of " spontaneous generation." The experi- 
ments of Pasteur and others showed that the germs of the 
yeast-plant may be disseminated by the atmosphere, and that 
the same precautions which exclude the introduction of germs 
from without into a fermentable liquid also exclude the process 



21 

of ferm'entation itself; so that we can now accept with confi- 
dence the double fact — 1. That the growth and reproduction 
of the yeast-fangus will take place only in a fermentable 
liquid ; and, 2. That .such a liquid will ferment only when 
the yeast-fungus is present and in a state of active develop- 
ment. 

The revolution in opinion on this point was so complete 
that, in regard to the alcoholic fermentation at least, its essen- 
tial results were finally accepted by Liebig himself. In his 
last treatise on fermentation, published in 1871, he says : ' 
" There no longer remains any doubt as to the nature of the 
ferment of beer and wine. It is a cryptogamic vegetation, 
more or less fully developed. . . . We may conclude that 
the albuminous matters of the yeast take part in its action 
upon the sugar, and it is evident that these albuminous matters 
acquire their property of exciting fermentation by becoming 
an actual constituent of the yeast itself." 

Consequently, the fermentation of a saccharine liquid is 
the result of vegetative activity. We add to the liquid a few 
cells or spores of the yeast-fungus. These grow and multiply, 
and the turbidity of the liquid is due to their increase and 
dissemination. They decompose its sugar, appropriate some 
of its elements, and leave as a result alcohol and carbonic acid. 
When all the sources of their nourishment are exhausted, fer- 
mentation stops, and the liquid becomes clear, the yeast- cells 
subsiding to the bottom. But the ferment has in the mean 
time been reproduced, like so much grain which has been sown, 
raised, and harvested; and a little of the deposit left at the 
bottom of the vessel, if introduced into another saccharine 
liquid, will in turn reproduce the process of fermentation. 

It is impossible not to perceive a certain analogy between 
the general phenomena of fermentation and those of conta- 
gious and infectious diseases. The period of incubation 
which intervenes between the exposure to a contagion and the 
appearance of the malady — the regular course of the symp- 
toms — their natural termination within a definite time, and 

1 '' Annalcs <lc Chiraie et de Physique," 1871, tome xxiii., pp. 9, 10. 



the evident reproduction of the contagious element — all these 
facts were so many points of resemblance, which could not 
escape the attention of medical observers. The analogy, in- 
deed, has long been recognized in our nomenclature ; and the 
term zymotic diseases cannot mean any thing else than dis- 
eases depending upon some cause which acts after the manner 
of a ferment. But this name was adopted only as a matter 
of convenience, and was understood altogether in a symbolical 
sense. Of late we have begun to suspect that, after all, it 
may be simply the expression of a literal fact. 

A similar order of discoveries has recently been made with 
regard to putrefaction. This has a more immediate connec- 
tion with pathology than fermentation, because it is a change 
which takes place in animal substances, while fermentation, 
at least in its simpler forms, relates mainly to products of a 
vegetable origin. 

Putrefaction was formerly regarded as the natural and 
inevitable decomposition of dead animal matter when exposed 
to the oxygen of the atmospheric air. But in reality some- 
thing else is necessary. In every putrefying liquid there are 
a growth and development of minute living organisms. If we 
take a clear solution of any nitrogenized animal or vegetable 
matter and expose it to the air at a moderate temperature, 
after a short time it becomes turbid. This turbidity is the 
first evidence of commencing putrefaction, and it is exactly 
analogous to the turbidity of a saccharine liquid which are 
beginning to ferment. Microscopic examination shows that 
it is due to the presence of innumerable bacterium-cells, -gj^-^ 
of an inch long, by ^."uinr °^ an " 1C ^ w ^ e ' movm g i n every 
direction, and multiplying by a rapid process of subdivision. 
As long as putrefaction goes on, so long the bacteria multiply. 
When it comes to an end the liquid becomes clear, and there 
is a quiescent layer of bacteria deposited upon the bottom. 
The least particle of this layer, added to another albuminous 
liquid, will excite putrefaction in it, and will produce a new 
development of bacterium-cells, the quantity of which is limited 
only by that of the albuminous matter which serves for their 
nourishment and growth. 



23 

Now, bacteria are the smallest and most obscure of living 
things. Their minute size alone is a sufficient obstacle, with 
our present microscopes, to their complete and satisfactory 
study in all particulars. Nevertheless, some important facts 
have been established with regard to them. In the first place, 
they are undoubtedly vegetable in their nature, and consist of 
cells which multiply by division, not by budding. They re- 
quire for their growth a temperature between the limits of 
freezing and boiling water. They consist of a protoplasmic 
matter, surrounded by an envelope of vegetable cellulose. 
They live upon nitrogenized and carbonaceous organic matters 
in solution, and, like other colorless plants, absorb oxygen 
and exhale carbonic acid. They present a variety of genera 
and species, which may be distinguished from each other with 
some approach to accuracy ; and, of these, Bacterium termo 
is the most constant and indispensable inhabitant of putrefying 
infusions. 

As to the true relations between bacteria and putrefaction, 
almost the same course of inquiry has been followed as in the 
case of the yeast-fungus and fermentation. At first regarded 
simply as an incidental accompaniment of the process, they 
are now considered as its essential and immediate cause. 
This view is distinctly stated by Dr. Ferdinand Cohn, to 
whom we owe more definite information on the natural 
history and microscopic characters of bacteria than to any 
other observer. Dr. Cohn is a professed scientific and ex- 
perimental botanist, and director of the Institute of Vegetable 
Physiology, at Breslau. He was the first to establish, twenty 
years ago, 1 the vegetable nature and structural relations of 
bacteria, and he has recently contributed largely to our knowl- 
edge of their classification and general physiology. 2 Accord- 
ing to him, the putrefaction of nitrogenous organic matters 
is neither a spontaneous post-mortem decomposition, nor is it 
a simple oxidation under the influence of the atmosphere. 
" It is rather a chemical process caused by the action of Bac- 

1 "Nova Acta Academiaj Carolo-Leopoldinas," lib. xxiv., p. 1. 
8 " Beitriige zur Biologie der Pflanzen," 1872, No. ii., p. 127. 



24 

teriurn termo. Just as sugar is never converted spontaneously 
into alcohol and carbonic acid, and is brought into fermen- 
tation only by the yeast-fungus, so nitrogenous organic matters 
never putrefy of themselves, but only by means of the vital 
activity and multiplication of bacteria. . . . "We may 
therefore," he says, "apply Pasteur's doctrine also to the 
decomposition of animal matters, and may adopt as true the 
seeming paradox that putrefaction is an incidental phe- 
nomenon, not of death, hut of vitality P 

The proof that living bacteria are the cause of putrefaction, 
and not merely its accompaniment, is that a putrescible liquid 
which has been sufficiently boiled and i-eceived in a super- 
heated glass vessel may be kept in contact with the atmos- 
phere indefinitely without putrefaction, provided the access of 
bacteria be prevented by a plug of cotton-wool. But, if the 
minutest portion of any liquid already infected with bacteria 
be added, putrefaction at once begins. Dr. Burdon-Sander- 
son, by a series of very important experiments in 1871, ' has 
established the fact, which is also confirmed by the researches 
of Cohn, 2 that contamination by the germs of bacteria takes 
place, as a general rule, not directly from the atmosphere, but 
by means of water and unclean moist surfaces ; while, on the 
other hand, the germs of the mould-fungi, like penicilium and 
mucor, are more or less constantly present in the air, and so 
readily gain access to organic substances, even in a dry atmos- 
phere. Consequently, such substances, if properly protected 
against bacteria, do not not putrefy, but, on the other hand, 
may become covered with a mould- fungus. Dr. Sanderson 
even cut out the muscular tissue of the thigh of a recently -killed 
Guinea-pig, and hung it up under a bell glass, using for this pur- 
pose a knife and hooks which had just been subjected to the 
flame of a Bunsen burner, but taking no other precautions ; 
and for thirty-one days, though the exposed tissues were over- 

1 " Thirteenth Report of the Medical Officer of the Privy Council," 
London, 1871. 

2 "Beitriige zur Biologie der Pflanzen," No. ii., p. 189. 



25 

grown with penicilium, there was no development of bacteria, 
and no evidence of putrefaction. 

The natural history of bacteria is especially connected with 
the question of spontaneous generation, because they are the 
only class of organisms now remaining in which reproduction 
by spores has not yet been discovered, and because they 
appear so promptly and abundantly in all putrescible liquids 
under ordinary exposures. 

Whatever may be the difference of opinion, therefore, with 
regard to the possibility of spontaneous generation within 
limited and exceptional conditions, there is hardly a doubt 
remaining that as a rule, in the regular operations of Nature, 
the bacteria or their germs are, in point of fact, conveyed from 
one putrefying substance to another, and that putrefaction is 
a process excited by contagion, and accomplished only by the 
growth and nutrition of bacteria. 

It was an important discovery when it was found, ten years 
ago, that bacteria might be developed in the interior of the 
living animal organism. In 1863 and 1864, Davaine ' showed 
that in the disease of sheep, known in France as " charbon " or 
" sang de rate," and called by the Germans " milz-brand," 
the blood of the affected animal, during life, contained bac- 
teria. He showed that the disease might be communicated by 
inoculation to other animals, always with a fatal result, and 
always with the development of bacteria in the blood previous 
to death. He afterward 2 extended the same observation to 
cases of malignant pustule, which he declared to be one form 
of the " sang de rate " disease. 

In 1868 Yulpian s found that a fatal disorder might be pro- 
duced in frogs by the administration of cyclamine ; that the 
malady was accompanied by the development of bacteria in 
the blood, and that inoculation of this blood reproduced the 
disease in other healthy animals of the same species. 

1 "Oomptes Rendus do l'Academie des Sciences," tomes lvi., lix. 

2 "Comptes Rendus," 18G5, tome lx., p. 1297. 

3 " Archives do Physiologic Normale et Pathologi<iue," 1868, p. 4G6. 



26 

About the same time, Professors Coze and Feltz, 1 formerly 
of the University of Strasbourg, had been making researches in 
a similar direction. They injected putrescent liquids into the 
veins or subcutaneous tissue in dogs and rabbits, producing in 
this way a fatal artificial septicaemia ; and they found that 
bacteria were developed in the blood of the animal simultane- 
ously with the appearance of the febrile condition. But the 
effect produced did not stop there. The blood of such an ani- 
mal, though not itself putrid, had become infectious, and 
would excite septicaemia in another animal by inoculation. 
A still farther remarkable result was obtained from these ex- 
periments : " By reproducing in this manner," the authors 
say, " several successive inoculations, it becomes evident that 
the infectious element is at last more active than the putres- 
cent matters themselves. Injection of putrescent liquids is 
not so rapidly fatal as inoculation of the blood of an animal 
already infected." 

These facts have been confirmed by the observations of 
Davaine and Vulpian, which show the extraordinary activity 
of infectious blood, even at a high degree of dilution. 
Davaine 2 found that putrefied bullock's blood, injected into 
the subcutaneous tissue of the rabbit, was rarely fatal in doses 
of less than -j-^ of a drop, and never so in less than ? t xh~o- But 
a series of twenty-five successive inoculations showed that 
septicaemia, once established, could be transmitted to the 
healthy rabbit by a dose of infectious blood so diluted that it 
represented only one trillion th part of a drop. Vulpian * 
injected a rabbit witli infectious serum, and produced death in 
twenty hours. A second rabbit was inoculated with the blood of 
the first, diluted to g^, and died in twenty-four hours. A third 
rabbit was inoculated with the blood of the second, diluted to 
T.irVs' an d died in twenty-three hours. A fourth animal, inocu- 
lated with the blood of the third, diluted to T.innf.Ttroj died i Q 

1 " Reclierches cliniques et experimentales sur les Maladies infectieuses," 
Paris, 1872. 

2 "Bulletin.de l'Academie de M6decine," Septembre 17, 1872. 

3 Gazette Medicale de Paris, 1873, No. 3, p. 30. 



27 

fifty- two hours ; while the fifth, inoculated with a dilution of 
T,innr,-m.iroT> became ill, but finally recovered. 

In cases of septicaemia, therefore, the bacteria really mul- 
tiply in the circulation during life ; and the small quantity of 
infectious blood necessary to produce the disease is explained 
by their singular activity of reproduction. 

These experiments certainly bring the study of morbid con- 
tagion into very close relationship with that of putrefaction 
and fermentation ; and there is no doubt that the analogies 
between them become more distinct and suggestive at every 
step of the investigation. It only remains to show that the 
same results will apply to diseases of more regular type and 
more familiar occurrence. 

If we were to choose any single morbid affection as a fair 
representative of the whole class of contagious disorders, I 
suppose small-pox would be the one selected. Its virulence, 
the certainty of its communication, the abundance of infec- 
tious matter generated, the regularity of its symptoms, and the 
definite periods of its incubation and development, all make 
it, so to speak, a kind of exponent of the essential qualities of 
infectious disease. Beside this, its singular relations to vaccine 
give it a peculiar interest ; and the vaccine affection also, 
though milder in its symptoms, is hardly less marked as a 
contagion than small-pox itself. Conclusions derived from ex- 
periments with either must be of great value in regard to the 
study of contagion as a whole. 

The first definite experiments in regard to the contagion of 
vaccine we owe, I think, to Chauveau. 1 He endeavored to as- 
certain whether the contagious principle of vaccine lymph 
were in its liquid or in its solid portions. For this purpose he 
treated vaccine lymph by the process of diffusion. The result 
showed that the contagious property of the lymph does not 
reside in its liquid part, but in its solid corpuscles and granu- 
lations. The liquid withdrawn by diffusion, though always 
found to contain abundance of albuminous matter in solution, 

1 "Comptes Eendus de 1'AcadGmie des Sciences," 1808, tome lxvi., p. 
289. 



2S 

failed when used for vaccination ; while that containing the 
solid granules possessed its normal activity and succeeded as 
fully as the fresh lymph. The results of these diffusion ex- 
periments were confirmed by those of Dr. Burdon-Sanderson, 1 
performed subsequently. 

Chauveau also adopted a second plan for investigating the 
same point, namely, that by dilution. The significance of 
this test depends on the following consideration : If the real 
vaccine virus be a fluid, it is of course uniformly distributed 
through all parts of the lymph ; and, if this lymph be diluted 
to any extent, the fluid virus will still be equally disseminated 
throughout the whole. When the dilution becomes so great 
as to extinguish the activity of the virus, this activity ought 
to diminish and disappear at the same time uniformly through 
all parts of the liquid. On the other hand, if the contagious 
principle reside in the solid particles, each one of which is 
capable of reproducing its kind, these particles will only be 
separated from each other by the dilution, and made less likely 
to be taken up in the drop used for vaccination. But, if one 
of them should be so taken up, it would still produce its full 
effect. In this case, the number of successful vaccinations 
would diminish in proportion to the dilution, and the number 
of failures would increase. But every vaccination which failed 
would fail completely, and every one which succeeded would 
produce a normal result. 

Chauveau's experiments showed that the latter supposition 
was correct. Yaccine lymph might be diluted with from two 
to eighteen times its weight of water without sensibly losing 
in efficacy ; and in one case the experimenter obtained a single 
pustule from a number of vaccinations made with lymph di- 
luted to y^-q-. He obtained, however, the most remarkable 
results with the lymph of sheep-pox, upon which he experi- 
mented largely. 2 He inoculated the same animal, by twenty- 
one punctures, with pock-lymph diluted to jfo ; and of these 

1 "Twelfth Eeport of the Medical Officer of the Privy Council," Lon- 
don, 1870, pp. 233, 235. 

s "Comptes Eendus," 1868, tome Ixvii., p. 749. 



29 

twenty-one inoculations eight failed, while thirteen gave origin 
to full-sized pustules. He then diluted the pock-lymph at once 
to ttt,^T¥? an d- "with t n ^ s diluted lymph, out of twenty inocu- 
lations he obtained only a single pustule, but that pustule pre- 
sented its normal features, and went through the usual stages 
of development. 

The active properties of the lymph of vaccine and variola, 
therefore, do not reside in its liquid ingredients, but in its solid 
corpuscles. These corpuscles, which were already observed by 
Chauveau and Burdon-Sanderson, have been recently exam- 
ined and described with great care by Dr. Colin. 1 This ob- 
server adopted every precaution against the introduction of 
foreign elements into the lymph. Some children with healthy 
vaccine vesicles were brought to the Botanical Institute, the 
vesicles opened with a new, unused lancet, the lymph taken 
up by aspiration in a recently-heated capillary glass tube, 
dropped upon a microscope-slide, and fitted with a glass cover, 
both the slide and cover having just been thoroughly cleansed 
with ammonia and boiling water. The edges of the cover 
were then lacquered down, to exclude the air, and the lymph- 
corpuscles examined at successive intervals of time. 

According to Dr. Cohn's observations, these corpuscles are 
single cells of a spherical form, not more than -g-^To °f an mcn 
in diameter. They belong to the genus Micrococcus, and 
those of the vaccine lymph are designated by the name of 
Micrococcus vaccinae. They increase in numbers if kept at 
the temperature of the living body, forming chains and groups 
of associated articulations. Dr. Cohn finds similar bodies in 
the fluid of small-pox vesicles, identical in size and appear- 
ance with those of the vaccine lymph. " We must, therefore," 
he says, " for the present regard the pock-lymph corpuscles as 
living and independent organisms, belonging to the smallest 
and simplest of all living things, which multiply, without 
formation of mycelium, by cell-division alone, and perhaps 
also by the production of resting spores." 

1 " Organisraen in der Pockcnlympbe." Archiv far pathologische Ana- 
tomic und Physiologies 1872, pp. 55, 229. 



30 

Finally, another kind of micrococcus lias been described 
by Dr. Oertel, 1 of Vienna, and by Prof. Ebert," of Zurich, as 
constantly present in cases of diphtheria ; and both observers 
have found that its inoculation in different parts of the body 
in healthy animals produces a diphtheritic malady, having its 
starting-point at the place of inoculation. 

The contributions to medical literature on this subject have 
increased of late with unusual rapidity. Since the beginning 
of 1870 more than two hundred distinct publications have 
made their appearance, either in the medical journals, or as 
separate volumes, on septicaemia and diphtheria, on micrococ- 
cus and bacteria, the ferment-corpuscles, fermentation and 
putrefaction, their relation to contagion and infection, and 
kindred topics. Many of these essays are extremely impor- 
tant, others of more or less doubtful value. I have not at- 
tempted to notice them all, but only those which seem to 
have really established some new facts relating to the origin 
and propagation of disease. Should the discoveries of the 
next ten years continue to lead in the direction now indicated, 
it will illustrate more fully than ever the intimate relation 
which exists between all the branches of medicine and natural 
science ; for it will show how large a part of human pathology 
is connected with the general physiology of vegetative life. 

1 " Deutsches Archiv fur klinische Medicin," 1871, B. viii., p. 242. 

2 " Zur Kentnis3 der bacteritischea Mykosen," Leipzig, 1872. 



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